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Full Paper
Ring-Closing Metathesis and Photo-Fries Reaction for the Construction of the Ansamycin Antibiotic Kendomycin: Development of a Protecting Group Free Oxidative Endgame
Article first published online: 30 NOV 2009
DOI: 10.1002/chem.200902226
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Magauer, T., Martin, H. and Mulzer, J. (2010), Ring-Closing Metathesis and Photo-Fries Reaction for the Construction of the Ansamycin Antibiotic Kendomycin: Development of a Protecting Group Free Oxidative Endgame. Chemistry - A European Journal, 16: 507–519. doi: 10.1002/chem.200902226
Publication History
- Issue published online: 28 DEC 2009
- Article first published online: 30 NOV 2009
- Manuscript Received: 10 AUG 2009
- Abstract
- Article
- References
- Cited By
Keywords:
- Claisen–Ireland rearrangement;
- metathesis;
- natural products;
- polyketides
Graphical Abstract
Underestimated: The thus far underestimated photo-Fries reaction serves as an efficient tool for the total synthesis of (−)-kendomycin. A powerful ring-closing metathesis is the basis of the second total synthesis. The installation of the lactol unit was performed by a chemoselective oxidation–hydrolysis sequence, thus avoiding additional protecting groups.
Abstract
Two convergent total syntheses of the ansa-polyketide (−)-kendomycin (1) are described. The syntheses benefit from the use of readily available and cheap starting materials. Highly complex diastereoselective Claisen–Ireland rearrangements were used to introduce the (E)-double bond and the C16-Me group. The ring closure of the strained ansa macrocycle was achieved by ring-closing metathesis and a highly efficient combination of macrolactonization and photo-Fries reaction. A protecting group free endgame via an unstable o-quinone is presented. Additionally some unsuccessful synthetic efforts towards the total synthesis of 1 are described.